Various devices and methods have been proposed for local application of a therapeutic agent or drug such as stents, vascular paving, and particle delivery. Stents are metallic or polymeric implantable structures that have been modified for local delivery of a drug. A polymer dissolved in a solvent including a drug can be applied to the stent. The solvent is removed, leaving behind a polymer coated stent capable of delivering a drug. A disadvantage of using a stent includes the trauma caused to the lumen, such as a blood vessel, during implantation of the stent. Radial pressure applied by the stent can lead to inflammation and tissue damage, which can cause the onset of restenosis or amplify the degree of vascular smooth muscle cell proliferation and migration. Hyper-proliferation and migration of vascular smooth muscle cells caused by the application of radial pressure by a stent can mitigate the effects of local therapeutic substance application.
For some applications such as vulnerable plaque, radial pressure applied by a stent can cause more sever damage than just inducement of restenosis. Unlike occlusive plaques that impede blood flow, vulnerable plaque develops within the arterial walls. Vulnerable plaque can exist without the symptomatic characteristic of a substantially narrow arterial lumen. The intrinsic histological features that may characterize a vulnerable plaque include increased lipid content, increased macrophage, foam cell and T lymphocyte content, and reduced collagen and smooth muscle cell content. This fibroatheroma type of vulnerable plaque is often referred to as “soft” collagen, whose reduced concentration combined with macrophage derived enzyme degradations cause the fibrous cap of these lesions to rupture under unpredictable circumstances. When ruptured, the lipid core contents, thought to include tissue factor, contact the arterial bloodstream, causing a blood clot to form that can completely block the artery resulting in acute coronary syndrome (ACS). This type of atherosclerosis is coined “vulnerable” because of unpredictable tendency of the plaque to rupture. It is thought that hemodynamic and cardiac forces, which yield to circumferential stress, shear stress, and flexation stress, may cause disruption of fibroatheroma type of vulnerable plaque. These forces may arise as the result of simple movements, such as getting out of bed in the morning, in vivo forces related to blood flow and the beating of the heart, as well as radial force applied by a stent. Accordingly, it is desirable to treat conditions such as vulnerable plaque with adequate source of drug delivery without the drawbacks associated with a stent.
Vascular paving can be performed by loading a monomer, pre-polymer or polymer in a balloon catheter, and then applying the composition directly to the inside of a tissue lumen within a zone occluded by the catheter balloon. The application can be through pores of the balloon, for example. The process is followed by curing or polymerizing the applied composition. The tissue surface may be an internal or external surface, and can include the interior of a tissue lumen or hollow space whether naturally occurring or occurring as a result of surgery, percutaneous techniques, trauma or disease. The polymeric material can be reconfigured to form a coating or “paving” layer in intimate and conforming contact with the surface. The resulting paving layer optionally can have a sealing function. The coating preferably has a thickness on the tissue surface on the order of 0.001-1.0 mm; however, coatings having a thickness outside that range may be used as well. By appropriate selection of the material employed and of the configuration of the paving material, the process can be tailored to satisfy a wide variety of biological or clinical situations. Drawbacks associated with vascular paving include the downstream flow and waste of the paving material prior to the curing of the composition and difficult and cumbersome procedural steps for the surgeon including the necessity to occlude the vessel in which the procedure is performed and the curing or polymerization of the polymer to achieve conformal coating about the location where its benefit is most desired. In sum, vascular paving has been considered a difficult procedure which can certainly out weight its benefits.
Particle drug delivery includes release of particles having a drug at the treatment site. If the particles are delivered so as to be embedded within the treatment site, they can cause sever trauma to the vessel, which would present the same issues as a stent as described above. If the particles are simply delivered without being embedded within the lumen, the therapeutic effect of the particles can depend on their size. Too small of particles can simply wash away with blood flow, resulting in negligible therapeutic treatment at the desired site. Moreover, other areas of the body not in need of treatment will be exposed to the drug, which in effect would be equivalent to systemic delivery of the drug. If the particles are too large, they form an embolus, causing cell damage or death.
It is desirable to address and treat vascular conditions, such as vulnerable plaque, a disease that is often seen in diabetics, with a use of a device that does not provide the above described drawbacks. It is also desirable to have a device which provides a sustained delivery of therapeutic agents to long or extended portions of coronary vessels or to a multitude of focal manifestations of a disease site. The use of the implantable device of the present invention, as can be appreciated by one having ordinary skill in the art, is certainly not limited to coronary vessels as it can have a multitude of applications in a variety of biological lumens and cavities.